The objectives of this Pathway to Independence Award for Karen M. Rodrigue, Ph.D., are to deepen the candidate's expertise in the field of cognitive neuroscience to enable her to investigate novel questions regarding the role of vascular risk in brain and cognitive aging. The central aim of this project is to examine a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of neural and cognitive aging within a normal aging model. The proposed K99 phase of research focuses on this aim by testing the hypothesis that age-related alteration in regional brain perfusion predicts decline in the cognitive performance of healthy middle-aged and older adults. The mentored phase also examines the modifying effects of hypertension on neural activity in an fMRI paradigm, testing the hypothesis that differences in vascular health can explain age-related dedifferentiation of brain function. A cross-sectional individual differences approach with a lifespan sample will be used to test hypotheses in the K99 phase. The R00 phase extends the study of the impact of vascular health on neural and cognitive decline by examining vascular predictors of [unreadable]-amyloid deposition in normal aging. The objectives of this research proposal are in accord with the mission of the National Institute on Aging. Understanding the contributions of vascular health to successful, as well as pathological aging is fundamentally important given both the prevalence of vascular risk in the aging population, and its amenability to prevention and treatment. The research skills and knowledge gained by the applicant during the completion of this project (e.g., training in fMRI, perfusion and PET imaging) along with the proposed coursework and professional development activities outlined in the training plan, will enable her to successfully transition to an independent position as a cognitive neuroscientist. PUBLIC HEALTH RELEVANCE: The present proposal examines a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of neural and cognitive aging within a normal aging model. Understanding the contributions of vascular health to successful, as well as pathological aging is fundamentally important given both the prevalence of vascular risk in the aging population, and its amenability to prevention and treatment.